Clinical Study to Evaluate the Efficacy and Safety of VR506 Using a New Inhaler for the Treatment of Asthma

Inclusion:

- Written informed consent

- Adolescents aged 12-17 years & adults aged 18-65 years (both inclusive)

- Documented clinical history of severe asthma requiring prednisone/prednisolone
therapy, high-intensity treatment ICS, OCS, LABA

- Stable OCS dose for ≥7 days before Screening Visit & during Screening Period.

- At least 80% compliant w/regular asthma medication per investigator at end of
Screening Period

- Documented asthma reversibility within 5 yrs prior to/during Screening Period, or
diagnosis of asthma that is incontrovertible per investigator

- Ability to use nDPI correctly, per investigator's review of completed inhaler
operation checklist

- Ability to use eDiary correctly, assessed by investigator at end of Screening Period

- Ability to comply w/study procedures, including blood sampling

- Ability to perform technically satisfactory pulmonary function tests

- Available to complete all study visits before 12 noon

- BMI of 16-26 kg/m2 in adolescents and 18-32 kg/m2 in adults

- Oral PIF ≥40 L/min, using an appropriate device set to match resistance of inhaler

- Good health, except for presence of asthma, per medical history/physical examination

- Negative drug/alcohol/urine cotinine screen. Subjects must test negative for
amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, ethanol
& opiates (unless given as prescription medicine)

- Non-smokers or ex-smokers with a smoking history of less than 10 pack-yrs (e.g. <20
cigarettes per day for 10 years or <40 cigarettes per day for 5 years) & stopped
smoking for at least 1 year prior to Screening Visit. Smoking will not be permitted
throughout study

- Female subjects of child-bearing potential must be using medically acceptable forms
of contraception [abstinence, hormonal (oral/implant/transdermal/injection), in use
for ≥3 consecutive months before first dose of study medication, double barrier
(condom w/spermicide, or diaphragm w/spermicide), IUD, or vasectomised partner (≥6
months since vasectomy)].

Exclusion:

- Regular use (≥3 times/wk) of topical steroids to treat dermatitis/rhinitis/allergic
conjunctivitis, within 28 days of Screening Visit

- Subjects who have/who have had, an upper/lower respiratory tract infection within 28
days of Screening Visit

- Subjects w/"brittle asthma

- Subjects w/asthma that required admission to an ICU and/or ventilation within
previous 12 months

- Subjects whose comorbidities, per investigator's opinion, are major contributors to
their respiratory symptoms (e.g. COPD, bronchiectasis, dysfunctional breathlessness,
vocal cord dysfunction, gastro-oesophageal reflux)

- Previously/currently diagnosed as having Churg-Strauss syndrome

- Previously/currently diagnosed as having pulmonary eosinophilia

- History of lung cancer

- Subjects w/current diagnosis of HIV infection

- Active chronic hepatitis B or C infection

- Subjects who have clinically significant abnormality/finding from examination, tests,
or history that may compromise subject safety, specifically any history of cardiac,
renal or hepatic impairment

- Subjects with an abnormal ECG

- Persistent arterial hypotension, with average SBP readings of ≤95 mmHg

- Persistent elevation of blood pressure, with average SBP readings of ≥160 mmHg or
average DBP readings of ≥100 mmHg

- Pregnant or lactating females

- Participation in another clinical study in 28 days prior to Screening Visit

- Evidence of clinically significant renal, hepatic, cardiac, pulmonary (apart from
asthma) or metabolic dysfunction, e.g. diabetes mellitus, thyrotoxicosis,
uncorrectable hypokalaemia, or predisposition to low levels of serum potassium

- Current/history of drug/alcohol abuse/dependence per WHO criteria

- Inability to communicate well w/investigator

- Donation of ≥450 mL of blood/blood products within previous 3 months prior to
screening

- History of allergy/intolerance/contraindications to corticosteroids/lactose, or
severe allergy to milk proteins

- Consumption of alcohol- or caffeine-containing foods/beverages from midnight before
or during Screening Visit

- History of medically diagnosed chronic respiratory diseases other than asthma (e.g.
chronic obstructive pulmonary disease, ABPA in the absence of asthma)